NAD-dependent methylenetetrahydrofolate dehydrogenase is expressed by immortal cells.
1985; Elsevier BV; Volume: 260; Issue: 27 Linguagem: Inglês
10.1016/s0021-9258(17)38612-x
ISSN1083-351X
AutoresNarciso R. Mejia, Robert E. MacKenzie,
Tópico(s)RNA modifications and cancer
ResumoY6 An enzyme activity not detected in normal cells is expressed in embryonic, undifferentiated, or transformed cells.Twenty-one established mammalian cell lines, both tumorigenic and nontumorigenic, were found to have an NAD-dependent methylenetetrahydrofolate dehydrogenase (Scrimgeour, K. G., and Huennekens, F. M. (1960) Biochern.Biophys.Res.Cornrnun.2, 230-233) in addition to the well-characterized NADP-specific activity.The NAD-dehydrogenase in cell extracts can be separated from the NADP activity by column chromatography.Normal adult tissues including brain, heart, skeletal muscle, liver, and kidney contain the NADP but not the NAD activity.Only normal tissues which contain differentiating cells such as bone marrow, thymus, spleen, and embryonic liver contain the NAD activity.The distribution of the NAD enzyme suggests that it could be useful as an oncodevelopmental marker.Its physiological role is unknown, but it is proposed that it promotes purine synthesis and perhaps contributes to the methionine dependence and rapid growth observed for many established lines.Cells are able to interconvert 10-formyltetrahydrofolate, required for purine biosynthesis, and methylenetetrahydrofolate (methylene-H4folate) used both for thymidylate synthesis and as a precursor to the methyl group of methionine.In mammalian cells this interconversion is catalyzed by NADP-dependent methylene-Hdolate dehydrogenase, which is found associated with methylene-Hrfolate cyclohydrolase and formyl-H4folate synthetase (see Ref. 1 for review).These three activities are properties of a single multifunctional protein that has been characterized from several species of mammalian liver as well as from yeast, and catalyzes the following reactions.methylene-Hrfolate + NADP+ t-)(1) methenyl-H4folate + NADPH methenyl-&folate + HzO t-) formyl-H4folate(2) formyl-H4folate + ADP + Pi -H4folate M%+(3)In microorganisms the dehydrogenase activity (Reaction 1) is
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